Publication: TRPV4 activation triggers the release of melatonin from human non-pigmented ciliary epithelial cells
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2015-07
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Elsevier
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Abstract
Melatonin is a neurohormone mainly produced in the pineal gland; nevertheless, various ocular structures such as the ciliary body, lens and the retina produce it. One of the roles of melatonin in the eye is the modulation of intraocular pressure, although little is known about the mechanisms that causes its presence in the aqueous humour. TRPV4 is a membrane channel which is activated by both physical and chemical stimuli. Therefore, this channel is sensitive to osmotic and hydrostatic pressure. As a consequence, TRPV4 results as an interesting candidate to study the relation between the activation of the TRPV4 channel and the production of melatonin. In this sense we have studied the role of the TRPV4 agonist GSK1016790A to modulate the production of melatonin in a cell line derived from human non-pigmented ciliary epithelial cells. The stimulation of the TRPV4 produced an increase in the extracellular melatonin levels changing from 8.5 ± 0.6 nM/well/30 min (control) to 23.3 ± 2.1 nM/well/30 min after 10 nM GSK1016790A application, this action being blocked by the selective antagonist RN 1734. The activation of the TRPV4 by GSK1016790A permitted to observe a melatonin increase which was concentration-dependent, and provided a pD2 value of −8.5 ± 0.1 (EC50 of 3.0 nM). In conclusion, the activation of the TRPV4 present in human non-pigmented ciliary epithelial cells can modulate the presence of extracellular melatonin, this being of relevance since this substance controls the dynamics of the aqueous humour.
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Received 11 December 2014; received in revised form 10 March 2015; accepted in revised form 27 April 2015; available online 29 April 2015.
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- Abe, M., Itoh, M.T., Miyata, M., Ishikawa, S., Sumi, Y., 1999. Detection of melatonin, its precursors and related enzyme activities in rabbit lens. Exp. Eye Res. 68, 255-262.
- Alarma-Estrany, P., Crooke, A., Pintor, J., 2009. 5-MCA-NAT does not act through NQO2 to reduce intraocular pressure in New-Zealand white rabbit. J. Pineal Res. 47, 201-209.
- Alarma-Estrany, P., Guzman-Aranguez, A., Huete, F., Peral, A., Plourde Jr., R., Pelaez, T., Yerxa, B., Pintor, J., 2011. Design of novel melatonin analogs for the reduction of intraocular pressure in normotensive rabbits. J. Pharmacol. Exp. Ther. 337, 703-709.
- Alarma-Estrany, P., Pintor, J., 2007. Melatonin receptors in the eye: location, second messengers and role in ocular physiology. Pharmacol. Ther. 113, 507-522.
- Chiquet, C., Claustrat, B., Thuret, G., Brun, J., Cooper, H.M., Denis, P., 2006. Melatonin concentrations in aqueous humor of glaucoma patients. Am. J. Ophthalmol. 142, 325-327.
- Garcia-Elias, A., Mrkonjic, S., Jung, C., Pardo-Pastor, C., Vicente, R., Valverde, M.A., 2014. The TRPV4 channel. Handb. Exp. Pharmacol. 222, 293-319.
- Hevia, D., Gonzalez-Menendez, P., Quiros-Gonz alez, I., Miar, A., Rodríguez-García, A., Tan, D.X., Reiter, R.J., Mayo, J.C., Sainz, R.M., 2015. Melatonin uptake through glucose transporters: a new target for melatonin inhibition of cancer. J. Pineal Res. 58 (2), 234-250.
- Huete-Toral, F., Crooke, A., Martinez-Aguila, A., Pintor, J., 2015. Melatonin receptors trigger cAMP production and inhibit chloride movements in nonpigmented ciliary epithelial cells. J. Pharmacol. Exp. Ther. 352, 119-128.
- Martin, X.D., Malina, H.Z., Brennan, M.C., Hendrickson, P.H., Lichter, P.R., 1992. The ciliary bodyethe third organ found to synthesize indoleamines in humans. Eur. J. Ophthalmol. 2, 67-72.
- McAlexander, M.A., Luttmann, M.A., Hunsberger, G.E., Undem, B.J., 2014. Transient receptor potential vanilloid 4 activation constricts the human bronchus via the release of cysteinyl leukotrienes. J. Pharmacol. Exp. Ther. 349, 118-125.
- Narita, K., Sasamoto, S., Koizumi, S., Okazaki, S., Nakamura, H., Inoue, T., Takeda, S., 2015. TRPV4 regulates the integrity of the blood-cerebrospinal fluid barrier and modulates transepithelial protein transport. FASEB J. fj.14e261396 (epub ahead of print).
- Osborne, N.N., 1994. Serotonin and melatonin in the iris/ciliary processes and their involvement in intraocular pressure. Acta Neurobiol. Exp. 54, 57-64.
- Pintor, J., Martin, L., Pelaez, T., Hoyle, C.H., Peral, A., 2001. Involvement of melatonin MT(3) receptors in the regulation of intraocular pressure in rabbits. Eur. J. Pharmacol. 416, 251-254.
- Rohde, B.H., McLaughlin, M.A., Chiou, L.Y., 1985. Existence and role of endogenous ocular melatonin. J. Ocul. Pharmacol. 1, 235-243.
- Samples, J.R., Krause, G., Lewy, A.J., 1988. Effect of melatonin on intraocular pressure. Curr. Eye Res. 7, 649-653.
- Thorneloe, K.S., Sulpizio, A.C., Lin, Z., Figueroa, D.J., Clouse, A.K., McCafferty, G.P., Chendrimada, T.P., Lashinger, E.S., Gordon, E., Evans, L., Misajet, B.A., Demarini, D.J., Nation, J.H., Casillas, L.N., Marquis, R.W., Votta, B.J., Sheardown, S.A., Xu, X., Brooks, D.P., Laping, N.J., Westfall, T.D., 2008. N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: Part I. J. Pharmacol. Exp. Ther. 326 (2), 432-442.
- Vincent, F., Acevedo, A., Nguyen, M.T., Dourado, M., DeFalco, J., Gustafson, A., Spiro, P., Emerling, D.E., Kelly, M.G., Duncton, M.A., 2009. Identification and characterization of novel TRPV4 modulators. Biochem.. Biophys. Res. Commun. 389, 490-494.